Full text data of ALDH1A1
ALDH1A1
(ALDC, ALDH1, PUMB1)
[Confidence: high (present in two of the MS resources)]
Retinal dehydrogenase 1; RALDH 1; RalDH1; 1.2.1.36 (ALDH-E1; ALHDII; Aldehyde dehydrogenase family 1 member A1; Aldehyde dehydrogenase, cytosolic)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Retinal dehydrogenase 1; RALDH 1; RalDH1; 1.2.1.36 (ALDH-E1; ALHDII; Aldehyde dehydrogenase family 1 member A1; Aldehyde dehydrogenase, cytosolic)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00218914
IPI00218914 Aldehyde dehydrogenase 1A1 oxidoreductase activity, metablism soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00218914 Aldehyde dehydrogenase 1A1 oxidoreductase activity, metablism soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P00352
ID AL1A1_HUMAN Reviewed; 501 AA.
AC P00352; O00768; Q5SYR1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 151.
DE RecName: Full=Retinal dehydrogenase 1;
DE Short=RALDH 1;
DE Short=RalDH1;
DE EC=1.2.1.36;
DE AltName: Full=ALDH-E1;
DE AltName: Full=ALHDII;
DE AltName: Full=Aldehyde dehydrogenase family 1 member A1;
DE AltName: Full=Aldehyde dehydrogenase, cytosolic;
GN Name=ALDH1A1; Synonyms=ALDC, ALDH1, PUMB1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2591967; DOI=10.1016/0888-7543(89)90127-4;
RA Hsu L.C., Chang W.-C., Yoshida A.;
RT "Genomic structure of the human cytosolic aldehyde dehydrogenase
RT gene.";
RL Genomics 5:857-865(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-121.
RC TISSUE=Liver;
RX PubMed=8214422; DOI=10.1111/j.1530-0277.1993.tb00849.x;
RA Zheng C.F., Wang T.T., Weiner H.;
RT "Cloning and expression of the full-length cDNAs encoding human liver
RT class 1 and class 2 aldehyde dehydrogenase.";
RL Alcohol. Clin. Exp. Res. 17:828-831(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lens;
RA Ramana K.V., Xiao T., Ansari N.H.;
RT "Cloning and expression of aldehyde dehydrogenase 1 (ALDH1A1) from
RT human lens cDNA library.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PHE-177.
RG NIEHS SNPs program;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6.
RX PubMed=8493914;
RA Yoshida A., Hsu L.C., Yanagawa Y.;
RT "Biological role of human cytosolic aldehyde dehydrogenase 1: hormonal
RT response, retinal oxidation and implication in testicular
RT feminization.";
RL Adv. Exp. Med. Biol. 328:37-44(1993).
RN [10]
RP PROTEIN SEQUENCE OF 2-501, AND ACETYLATION AT SER-2.
RC TISSUE=Liver;
RX PubMed=6723659; DOI=10.1111/j.1432-1033.1984.tb08150.x;
RA Hempel J., von Bahr-Lindstroem H., Joernvall H.;
RT "Aldehyde dehydrogenase from human liver. Primary structure of the
RT cytoplasmic isoenzyme.";
RL Eur. J. Biochem. 141:21-35(1984).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 162-501.
RX PubMed=4015823; DOI=10.1016/0741-8329(85)90024-2;
RA Yoshida A., Ikawa M., Hsu L.C., Tani K.;
RT "Molecular abnormality and cDNA cloning of human aldehyde
RT dehydrogenases.";
RL Alcohol 2:103-106(1985).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 162-501.
RC TISSUE=Liver;
RX PubMed=2987944; DOI=10.1073/pnas.82.11.3771;
RA Hsu L.C., Tani K., Fujiyoshi T., Kurachi K., Yoshida A.;
RT "Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:3771-3775(1985).
RN [13]
RP PROTEIN SEQUENCE OF 266-273, ACTIVE SITES GLU-269 AND CYS-303, AND
RP NAD-BINDING SITE CYS-456.
RX PubMed=3676276; DOI=10.1021/bi00392a015;
RA Abriola D.P., Fields R., Stein S., Mackerell A.D. Jr., Pietruszko R.;
RT "Active site of human liver aldehyde dehydrogenase.";
RL Biochemistry 26:5679-5684(1987).
RN [14]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Erythrocyte;
RX PubMed=2776714;
RA Agarwal D.P., Cohn P., Goedde H.W., Hempel J.;
RT "Aldehyde dehydrogenase from human erythrocytes: structural
RT relationship to the liver cytosolic isozyme.";
RL Enzyme 42:47-52(1989).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-91; LYS-128; LYS-252;
RP LYS-353; LYS-367; LYS-410; LYS-419; LYS-435 AND LYS-495, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Binds free retinal and cellular retinol-binding protein-
CC bound retinal. Can convert/oxidize retinaldehyde to retinoic acid
CC (By similarity).
CC -!- CATALYTIC ACTIVITY: Retinal + NAD(+) + H(2)O = retinoate + NADH.
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/aldh1a1/";
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DR EMBL; M31994; AAA51692.1; -; Genomic_DNA.
DR EMBL; M31982; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31983; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31984; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31985; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31986; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31987; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31988; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31989; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31990; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31991; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31992; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; AF003341; AAC51652.1; -; mRNA.
DR EMBL; AY390731; AAR92229.1; -; mRNA.
DR EMBL; BT006921; AAP35567.1; -; mRNA.
DR EMBL; AY338497; AAP88039.1; -; Genomic_DNA.
DR EMBL; AL591031; CAI12257.1; -; Genomic_DNA.
DR EMBL; CH471089; EAW62543.1; -; Genomic_DNA.
DR EMBL; BC001505; AAH01505.1; -; mRNA.
DR EMBL; S61235; AAD13925.1; -; Genomic_DNA.
DR EMBL; M26761; AAA35518.1; -; mRNA.
DR EMBL; K03000; AAA51695.1; -; mRNA.
DR PIR; A33371; DEHUE1.
DR RefSeq; NP_000680.2; NM_000689.4.
DR RefSeq; XP_005251857.1; XM_005251800.1.
DR UniGene; Hs.76392; -.
DR ProteinModelPortal; P00352; -.
DR SMR; P00352; 8-501.
DR IntAct; P00352; 6.
DR MINT; MINT-4999613; -.
DR STRING; 9606.ENSP00000297785; -.
DR BindingDB; P00352; -.
DR ChEMBL; CHEMBL3577; -.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB00755; Tretinoin.
DR DrugBank; DB00162; Vitamin A.
DR PhosphoSite; P00352; -.
DR DMDM; 118495; -.
DR DOSAC-COBS-2DPAGE; P00352; -.
DR REPRODUCTION-2DPAGE; IPI00218914; -.
DR REPRODUCTION-2DPAGE; P00352; -.
DR SWISS-2DPAGE; P00352; -.
DR UCD-2DPAGE; P00352; -.
DR PaxDb; P00352; -.
DR PeptideAtlas; P00352; -.
DR PRIDE; P00352; -.
DR DNASU; 216; -.
DR Ensembl; ENST00000297785; ENSP00000297785; ENSG00000165092.
DR GeneID; 216; -.
DR KEGG; hsa:216; -.
DR UCSC; uc004ajd.3; human.
DR CTD; 216; -.
DR GeneCards; GC09M075515; -.
DR HGNC; HGNC:402; ALDH1A1.
DR HPA; CAB020690; -.
DR HPA; HPA002123; -.
DR MIM; 100640; gene.
DR neXtProt; NX_P00352; -.
DR PharmGKB; PA24692; -.
DR eggNOG; COG1012; -.
DR HOGENOM; HOG000271505; -.
DR HOVERGEN; HBG000097; -.
DR InParanoid; P00352; -.
DR KO; K07249; -.
DR OMA; YMGSLIK; -.
DR OrthoDB; EOG7PS1F7; -.
DR PhylomeDB; P00352; -.
DR BioCyc; MetaCyc:HS09183-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P00352; -.
DR UniPathway; UPA00912; -.
DR ChiTaRS; ALDH1A1; human.
DR GeneWiki; ALDH1A1; -.
DR GenomeRNAi; 216; -.
DR NextBio; 874; -.
DR PRO; PR:P00352; -.
DR ArrayExpress; P00352; -.
DR Bgee; P00352; -.
DR CleanEx; HS_ALDH1A1; -.
DR Genevestigator; P00352; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD) activity; EXP:Reactome.
DR GO; GO:0005497; F:androgen binding; TAS:ProtInc.
DR GO; GO:0005099; F:Ras GTPase activator activity; TAS:UniProtKB.
DR GO; GO:0001758; F:retinal dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; TAS:ProtInc.
DR GO; GO:0006069; P:ethanol oxidation; TAS:Reactome.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 1.
DR InterPro; IPR016161; Ald_DH/histidinol_DH.
DR InterPro; IPR016163; Ald_DH_C.
DR InterPro; IPR016160; Ald_DH_CS.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing;
KW NAD; Oxidoreductase; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 501 Retinal dehydrogenase 1.
FT /FTId=PRO_0000056415.
FT NP_BIND 246 251 NAD (By similarity).
FT ACT_SITE 269 269 Proton acceptor.
FT ACT_SITE 303 303 Nucleophile.
FT BINDING 456 456 NAD.
FT SITE 170 170 Transition state stabilizer (By
FT similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 91 91 N6-acetyllysine.
FT MOD_RES 128 128 N6-acetyllysine.
FT MOD_RES 252 252 N6-acetyllysine.
FT MOD_RES 353 353 N6-acetyllysine.
FT MOD_RES 367 367 N6-acetyllysine.
FT MOD_RES 410 410 N6-acetyllysine.
FT MOD_RES 419 419 N6-acetyllysine.
FT MOD_RES 435 435 N6-acetyllysine.
FT MOD_RES 495 495 N6-acetyllysine.
FT VARIANT 121 121 N -> S (in dbSNP:rs1049981).
FT /FTId=VAR_048901.
FT VARIANT 125 125 G -> R (in dbSNP:rs11554423).
FT /FTId=VAR_048902.
FT VARIANT 177 177 I -> F (in dbSNP:rs8187929).
FT /FTId=VAR_017778.
FT CONFLICT 162 162 V -> I (in Ref. 11; AAA35518 and 12;
FT AAA51695).
SQ SEQUENCE 501 AA; 54862 MW; B26464DC7168348E CRC64;
MSSSGTPDLP VLLTDLKIQY TKIFINNEWH DSVSGKKFPV FNPATEEELC QVEEGDKEDV
DKAVKAARQA FQIGSPWRTM DASERGRLLY KLADLIERDR LLLATMESMN GGKLYSNAYL
NDLAGCIKTL RYCAGWADKI QGRTIPIDGN FFTYTRHEPI GVCGQIIPWN FPLVMLIWKI
GPALSCGNTV VVKPAEQTPL TALHVASLIK EAGFPPGVVN IVPGYGPTAG AAISSHMDID
KVAFTGSTEV GKLIKEAAGK SNLKRVTLEL GGKSPCIVLA DADLDNAVEF AHHGVFYHQG
QCCIAASRIF VEESIYDEFV RRSVERAKKY ILGNPLTPGV TQGPQIDKEQ YDKILDLIES
GKKEGAKLEC GGGPWGNKGY FVQPTVFSNV TDEMRIAKEE IFGPVQQIMK FKSLDDVIKR
ANNTFYGLSA GVFTKDIDKA ITISSALQAG TVWVNCYGVV SAQCPFGGFK MSGNGRELGE
YGFHEYTEVK TVTVKISQKN S
//
ID AL1A1_HUMAN Reviewed; 501 AA.
AC P00352; O00768; Q5SYR1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 151.
DE RecName: Full=Retinal dehydrogenase 1;
DE Short=RALDH 1;
DE Short=RalDH1;
DE EC=1.2.1.36;
DE AltName: Full=ALDH-E1;
DE AltName: Full=ALHDII;
DE AltName: Full=Aldehyde dehydrogenase family 1 member A1;
DE AltName: Full=Aldehyde dehydrogenase, cytosolic;
GN Name=ALDH1A1; Synonyms=ALDC, ALDH1, PUMB1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2591967; DOI=10.1016/0888-7543(89)90127-4;
RA Hsu L.C., Chang W.-C., Yoshida A.;
RT "Genomic structure of the human cytosolic aldehyde dehydrogenase
RT gene.";
RL Genomics 5:857-865(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-121.
RC TISSUE=Liver;
RX PubMed=8214422; DOI=10.1111/j.1530-0277.1993.tb00849.x;
RA Zheng C.F., Wang T.T., Weiner H.;
RT "Cloning and expression of the full-length cDNAs encoding human liver
RT class 1 and class 2 aldehyde dehydrogenase.";
RL Alcohol. Clin. Exp. Res. 17:828-831(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lens;
RA Ramana K.V., Xiao T., Ansari N.H.;
RT "Cloning and expression of aldehyde dehydrogenase 1 (ALDH1A1) from
RT human lens cDNA library.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PHE-177.
RG NIEHS SNPs program;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E.,
RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S.,
RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R.,
RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W.,
RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G.,
RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M.,
RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W.,
RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A.,
RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J.,
RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M.,
RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S.,
RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J.,
RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R.,
RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M.,
RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M.,
RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A.,
RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W.,
RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S.,
RA Rogers J., Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6.
RX PubMed=8493914;
RA Yoshida A., Hsu L.C., Yanagawa Y.;
RT "Biological role of human cytosolic aldehyde dehydrogenase 1: hormonal
RT response, retinal oxidation and implication in testicular
RT feminization.";
RL Adv. Exp. Med. Biol. 328:37-44(1993).
RN [10]
RP PROTEIN SEQUENCE OF 2-501, AND ACETYLATION AT SER-2.
RC TISSUE=Liver;
RX PubMed=6723659; DOI=10.1111/j.1432-1033.1984.tb08150.x;
RA Hempel J., von Bahr-Lindstroem H., Joernvall H.;
RT "Aldehyde dehydrogenase from human liver. Primary structure of the
RT cytoplasmic isoenzyme.";
RL Eur. J. Biochem. 141:21-35(1984).
RN [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 162-501.
RX PubMed=4015823; DOI=10.1016/0741-8329(85)90024-2;
RA Yoshida A., Ikawa M., Hsu L.C., Tani K.;
RT "Molecular abnormality and cDNA cloning of human aldehyde
RT dehydrogenases.";
RL Alcohol 2:103-106(1985).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 162-501.
RC TISSUE=Liver;
RX PubMed=2987944; DOI=10.1073/pnas.82.11.3771;
RA Hsu L.C., Tani K., Fujiyoshi T., Kurachi K., Yoshida A.;
RT "Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:3771-3775(1985).
RN [13]
RP PROTEIN SEQUENCE OF 266-273, ACTIVE SITES GLU-269 AND CYS-303, AND
RP NAD-BINDING SITE CYS-456.
RX PubMed=3676276; DOI=10.1021/bi00392a015;
RA Abriola D.P., Fields R., Stein S., Mackerell A.D. Jr., Pietruszko R.;
RT "Active site of human liver aldehyde dehydrogenase.";
RL Biochemistry 26:5679-5684(1987).
RN [14]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Erythrocyte;
RX PubMed=2776714;
RA Agarwal D.P., Cohn P., Goedde H.W., Hempel J.;
RT "Aldehyde dehydrogenase from human erythrocytes: structural
RT relationship to the liver cytosolic isozyme.";
RL Enzyme 42:47-52(1989).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-91; LYS-128; LYS-252;
RP LYS-353; LYS-367; LYS-410; LYS-419; LYS-435 AND LYS-495, AND MASS
RP SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Binds free retinal and cellular retinol-binding protein-
CC bound retinal. Can convert/oxidize retinaldehyde to retinoic acid
CC (By similarity).
CC -!- CATALYTIC ACTIVITY: Retinal + NAD(+) + H(2)O = retinoate + NADH.
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the aldehyde dehydrogenase family.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/aldh1a1/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; M31994; AAA51692.1; -; Genomic_DNA.
DR EMBL; M31982; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31983; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31984; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31985; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31986; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31987; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31988; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31989; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31990; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31991; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; M31992; AAA51692.1; JOINED; Genomic_DNA.
DR EMBL; AF003341; AAC51652.1; -; mRNA.
DR EMBL; AY390731; AAR92229.1; -; mRNA.
DR EMBL; BT006921; AAP35567.1; -; mRNA.
DR EMBL; AY338497; AAP88039.1; -; Genomic_DNA.
DR EMBL; AL591031; CAI12257.1; -; Genomic_DNA.
DR EMBL; CH471089; EAW62543.1; -; Genomic_DNA.
DR EMBL; BC001505; AAH01505.1; -; mRNA.
DR EMBL; S61235; AAD13925.1; -; Genomic_DNA.
DR EMBL; M26761; AAA35518.1; -; mRNA.
DR EMBL; K03000; AAA51695.1; -; mRNA.
DR PIR; A33371; DEHUE1.
DR RefSeq; NP_000680.2; NM_000689.4.
DR RefSeq; XP_005251857.1; XM_005251800.1.
DR UniGene; Hs.76392; -.
DR ProteinModelPortal; P00352; -.
DR SMR; P00352; 8-501.
DR IntAct; P00352; 6.
DR MINT; MINT-4999613; -.
DR STRING; 9606.ENSP00000297785; -.
DR BindingDB; P00352; -.
DR ChEMBL; CHEMBL3577; -.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB00755; Tretinoin.
DR DrugBank; DB00162; Vitamin A.
DR PhosphoSite; P00352; -.
DR DMDM; 118495; -.
DR DOSAC-COBS-2DPAGE; P00352; -.
DR REPRODUCTION-2DPAGE; IPI00218914; -.
DR REPRODUCTION-2DPAGE; P00352; -.
DR SWISS-2DPAGE; P00352; -.
DR UCD-2DPAGE; P00352; -.
DR PaxDb; P00352; -.
DR PeptideAtlas; P00352; -.
DR PRIDE; P00352; -.
DR DNASU; 216; -.
DR Ensembl; ENST00000297785; ENSP00000297785; ENSG00000165092.
DR GeneID; 216; -.
DR KEGG; hsa:216; -.
DR UCSC; uc004ajd.3; human.
DR CTD; 216; -.
DR GeneCards; GC09M075515; -.
DR HGNC; HGNC:402; ALDH1A1.
DR HPA; CAB020690; -.
DR HPA; HPA002123; -.
DR MIM; 100640; gene.
DR neXtProt; NX_P00352; -.
DR PharmGKB; PA24692; -.
DR eggNOG; COG1012; -.
DR HOGENOM; HOG000271505; -.
DR HOVERGEN; HBG000097; -.
DR InParanoid; P00352; -.
DR KO; K07249; -.
DR OMA; YMGSLIK; -.
DR OrthoDB; EOG7PS1F7; -.
DR PhylomeDB; P00352; -.
DR BioCyc; MetaCyc:HS09183-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P00352; -.
DR UniPathway; UPA00912; -.
DR ChiTaRS; ALDH1A1; human.
DR GeneWiki; ALDH1A1; -.
DR GenomeRNAi; 216; -.
DR NextBio; 874; -.
DR PRO; PR:P00352; -.
DR ArrayExpress; P00352; -.
DR Bgee; P00352; -.
DR CleanEx; HS_ALDH1A1; -.
DR Genevestigator; P00352; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004029; F:aldehyde dehydrogenase (NAD) activity; EXP:Reactome.
DR GO; GO:0005497; F:androgen binding; TAS:ProtInc.
DR GO; GO:0005099; F:Ras GTPase activator activity; TAS:UniProtKB.
DR GO; GO:0001758; F:retinal dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0006081; P:cellular aldehyde metabolic process; TAS:ProtInc.
DR GO; GO:0006069; P:ethanol oxidation; TAS:Reactome.
DR GO; GO:0042572; P:retinol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006805; P:xenobiotic metabolic process; TAS:Reactome.
DR Gene3D; 3.40.309.10; -; 1.
DR Gene3D; 3.40.605.10; -; 1.
DR InterPro; IPR016161; Ald_DH/histidinol_DH.
DR InterPro; IPR016163; Ald_DH_C.
DR InterPro; IPR016160; Ald_DH_CS.
DR InterPro; IPR016162; Ald_DH_N.
DR InterPro; IPR015590; Aldehyde_DH_dom.
DR Pfam; PF00171; Aldedh; 1.
DR SUPFAM; SSF53720; SSF53720; 1.
DR PROSITE; PS00070; ALDEHYDE_DEHYDR_CYS; 1.
DR PROSITE; PS00687; ALDEHYDE_DEHYDR_GLU; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing;
KW NAD; Oxidoreductase; Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 501 Retinal dehydrogenase 1.
FT /FTId=PRO_0000056415.
FT NP_BIND 246 251 NAD (By similarity).
FT ACT_SITE 269 269 Proton acceptor.
FT ACT_SITE 303 303 Nucleophile.
FT BINDING 456 456 NAD.
FT SITE 170 170 Transition state stabilizer (By
FT similarity).
FT MOD_RES 2 2 N-acetylserine.
FT MOD_RES 91 91 N6-acetyllysine.
FT MOD_RES 128 128 N6-acetyllysine.
FT MOD_RES 252 252 N6-acetyllysine.
FT MOD_RES 353 353 N6-acetyllysine.
FT MOD_RES 367 367 N6-acetyllysine.
FT MOD_RES 410 410 N6-acetyllysine.
FT MOD_RES 419 419 N6-acetyllysine.
FT MOD_RES 435 435 N6-acetyllysine.
FT MOD_RES 495 495 N6-acetyllysine.
FT VARIANT 121 121 N -> S (in dbSNP:rs1049981).
FT /FTId=VAR_048901.
FT VARIANT 125 125 G -> R (in dbSNP:rs11554423).
FT /FTId=VAR_048902.
FT VARIANT 177 177 I -> F (in dbSNP:rs8187929).
FT /FTId=VAR_017778.
FT CONFLICT 162 162 V -> I (in Ref. 11; AAA35518 and 12;
FT AAA51695).
SQ SEQUENCE 501 AA; 54862 MW; B26464DC7168348E CRC64;
MSSSGTPDLP VLLTDLKIQY TKIFINNEWH DSVSGKKFPV FNPATEEELC QVEEGDKEDV
DKAVKAARQA FQIGSPWRTM DASERGRLLY KLADLIERDR LLLATMESMN GGKLYSNAYL
NDLAGCIKTL RYCAGWADKI QGRTIPIDGN FFTYTRHEPI GVCGQIIPWN FPLVMLIWKI
GPALSCGNTV VVKPAEQTPL TALHVASLIK EAGFPPGVVN IVPGYGPTAG AAISSHMDID
KVAFTGSTEV GKLIKEAAGK SNLKRVTLEL GGKSPCIVLA DADLDNAVEF AHHGVFYHQG
QCCIAASRIF VEESIYDEFV RRSVERAKKY ILGNPLTPGV TQGPQIDKEQ YDKILDLIES
GKKEGAKLEC GGGPWGNKGY FVQPTVFSNV TDEMRIAKEE IFGPVQQIMK FKSLDDVIKR
ANNTFYGLSA GVFTKDIDKA ITISSALQAG TVWVNCYGVV SAQCPFGGFK MSGNGRELGE
YGFHEYTEVK TVTVKISQKN S
//
MIM
100640
*RECORD*
*FIELD* NO
100640
*FIELD* TI
*100640 ALDEHYDE DEHYDROGENASE 1 FAMILY, MEMBER A1; ALDH1A1
;;ALDEHYDE DEHYDROGENASE 1; ALDH1;;
read moreACETALDEHYDE DEHYDROGENASE 1;;
ALDH, LIVER CYTOSOLIC;;
RETINAL DEHYDROGENASE 1; RALDH1
*FIELD* TX
DESCRIPTION
The ALDH1A1 gene encodes a liver cytosolic isoform of acetaldehyde
dehydrogenase (EC 1.2.1.3), an enzyme involved in the major pathway of
alcohol metabolism after alcohol dehydrogenase (ADH, see 103700). See
also liver mitochondrial ALDH2 (100650), variation in which has been
implicated in different responses to alcohol ingestion.
ALDH1 is associated with a low Km for NAD, a high Km for acetaldehyde,
and is strongly inactivated by disulfiram. ALDH2 is associated with a
high Km for NAD, and low Km for acetaldehyde, and is insensitive to
inhibition by disulfiram (Hsu et al., 1985).
CLONING
Inoue et al. (1979) purified and partially characterized aldehyde
dehydrogenase from human erythrocytes: this was the cytosolic form,
present in only low concentration in red cells. Using isoelectric
focusing, Thomas et al. (1982) showed that the cytosolic and
mitochondrial ALDHs are distinct isozymes. Hempel et al. (1984)
determined the amino acid sequence of the cytosolic ALDH isoform. The
monomer is composed of 500 residues and contains 11 cysteine residues.
Hsu et al. (1985) reported cloning of the ALDH1 and ALDH2 genes. The 2
proteins showed 69% homology at the protein level. The ALDH1 gene
encodes a 501-residue protein (Hsu et al., 1989).
MAPPING
With cDNA probes for Southern blot analysis of somatic cell hybrids, Hsu
et al. (1985, 1986) assigned the ALDH1 locus to chromosome 9q and the
ALDH2 locus to chromosome 12.
GENE STRUCTURE
Hsu et al. (1989) found that the ALDH1 gene is about 53 kb long and is
divided into 13 exons. A similar intron-exon organization was found in
ALDH2, which also has 13 exons with 9 of the 12 introns interrupting the
coding sequence at positions homologous to those in ALDH1. Thus, the 2
isozymes appear to have evolved after duplication of a common ancestral
gene.
MOLECULAR GENETICS
Thomas et al. (1982) found low cytosolic ALDH in the liver of alcoholic
patients with fatty liver; mitochondrial ALDH was normal. Abstaining
alcoholics showed persistently low cytosolic ALDH.
Eckey et al. (1986) reported a variant of cytosolic ALDH in a Chinese
autopsy liver specimen. While the major isozyme band was nearly absent,
several additional minor bands were observed on isoelectric focusing
gel. Rabbit antibodies showed immunological cross-reactivity for the
variant enzyme bands. The existence of additional minor bands indicated
the presence of tetramer hybrid forms made up of normal and variant
monomers. The observed abnormality may represent a heterozygous form of
cytosolic ALDH variation. A similar variant was also detected in
erythrocytes of a male Thai student.
Yoshida et al. (1989) demonstrated that among Caucasians alcohol
flushing can be related to abnormalities of ALDH1. In 9 unrelated
Caucasian alcohol flushers, they found 1 who exhibited low activity
(10-20% of normal) and another who exhibited moderately low activity
(60%) and altered kinetic properties. The electrophoretic mobilities of
these 2 samples were not altered. Immunologic quantitation indicated
that the amount of protein in the 2 samples was not reduced in parallel
with the enzyme deficiency. In the first case, the daughter of the
proposita also had very low enzyme activity and alcohol flushing.
ANIMAL MODEL
Retinaldehyde is generated by ADH1 (103700) from retinol, and its
concentration is determined in large part by its subsequent catabolism
by RALDH1 to retinoic acid. Ziouzenkova et al. (2007) demonstrated that
retinaldehyde is present in rodent fat, binds retinol-binding proteins
(CRBP1, 180260; RBP4, 180250), and suppresses PPARG (601487) and
retinoid X receptor (see 180245) responses. Raldh1 -/- mice resisted
diet-induced obesity and insulin resistance and showed increased energy
dissipation. In ob/ob (see 164160) mice, administering retinaldehyde or
a Raldh inhibitor reduced fat and increased insulin sensitivity.
Ziouzenkova et al. (2007) concluded that retinaldehyde is a distinct
transcriptional regulator of the metabolic responses to a high-fat diet.
*FIELD* RF
1. Eckey, R.; Agarwal, D. P.; Saha, N.; Goedde, H. W.: Detection
and partial characterization of a variant form of cytosolic aldehyde
dehydrogenase isozyme. Hum. Genet. 72: 95-97, 1986.
2. Hempel, J.; von Bahr-Lindstrom, H.; Jornvall, H.: Aldehyde dehydrogenase
from human liver: primary structure of the cytoplasmic isoenzyme. Europ.
J. Biochem. 141: 21-35, 1984.
3. Hsu, L. C.; Chang, W.-C.; Yoshida, A.: Genomic structure of the
human cytosolic aldehyde dehydrogenase gene. Genomics 5: 857-865,
1989.
4. Hsu, L. C.; Tani, K.; Fujiyoshi, T.; Kurachi, K.; Yoshida, A.:
Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2. Proc.
Nat. Acad. Sci. 82: 3771-3775, 1985.
5. Hsu, L. C.; Yoshida, A.; Mohandas, T.: Chromosomal assignment
of the genes for human aldehyde dehydrogenase-1 and aldehyde dehydrogenase-2. Am.
J. Hum. Genet. 38: 641-648, 1986.
6. Inoue, K.; Nishimukai, H.; Yamasawa, K.: Purification and partial
characterization of aldehyde dehydrogenase from human erythrocytes. Biochim.
Biophys. Acta 569: 117-123, 1979.
7. Thomas, M.; Halsall, S.; Peters, T. J.: Role of hepatic acetaldehyde
dehydrogenase in alcoholism: demonstration of persistent reduction
of cytosolic activity in abstaining patients. Lancet II: 1057-1059,
1982.
8. Yoshida, A.; Dave, V.; Ward, R. J.; Peters, T. J.: Cytosolic aldehyde
dehydrogenase (ALDH1) variants found in alcohol flushers. Ann. Hum.
Genet. 53: 1-7, 1989.
9. Ziouzenkova, O.; Orasanu, G.; Sharlach, M.; Akiyama, T. E.; Berger,
J. P.; Viereck, J.; Hamilton, J. A.; Tang, G.; Dolnikowski, G. G.;
Vogel, S.; Duester, G.; Plutzky, J.: Retinaldehyde represses adipogenesis
and diet-induced obesity. Nature Med. 13: 695-702, 2007.
*FIELD* CN
Marla J. F. O'Neill - updated: 7/2/2007
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
ckniffin: 10/21/2009
terry: 1/7/2009
wwang: 7/5/2007
terry: 7/2/2007
alopez: 2/3/2006
mgross: 11/19/2001
carol: 4/3/2001
dkim: 7/17/1998
dkim: 6/26/1998
jenny: 7/2/1997
jenny: 7/1/1997
mimadm: 3/11/1994
supermim: 3/16/1992
carol: 2/29/1992
supermim: 3/20/1990
carol: 12/14/1989
carol: 11/2/1989
*RECORD*
*FIELD* NO
100640
*FIELD* TI
*100640 ALDEHYDE DEHYDROGENASE 1 FAMILY, MEMBER A1; ALDH1A1
;;ALDEHYDE DEHYDROGENASE 1; ALDH1;;
read moreACETALDEHYDE DEHYDROGENASE 1;;
ALDH, LIVER CYTOSOLIC;;
RETINAL DEHYDROGENASE 1; RALDH1
*FIELD* TX
DESCRIPTION
The ALDH1A1 gene encodes a liver cytosolic isoform of acetaldehyde
dehydrogenase (EC 1.2.1.3), an enzyme involved in the major pathway of
alcohol metabolism after alcohol dehydrogenase (ADH, see 103700). See
also liver mitochondrial ALDH2 (100650), variation in which has been
implicated in different responses to alcohol ingestion.
ALDH1 is associated with a low Km for NAD, a high Km for acetaldehyde,
and is strongly inactivated by disulfiram. ALDH2 is associated with a
high Km for NAD, and low Km for acetaldehyde, and is insensitive to
inhibition by disulfiram (Hsu et al., 1985).
CLONING
Inoue et al. (1979) purified and partially characterized aldehyde
dehydrogenase from human erythrocytes: this was the cytosolic form,
present in only low concentration in red cells. Using isoelectric
focusing, Thomas et al. (1982) showed that the cytosolic and
mitochondrial ALDHs are distinct isozymes. Hempel et al. (1984)
determined the amino acid sequence of the cytosolic ALDH isoform. The
monomer is composed of 500 residues and contains 11 cysteine residues.
Hsu et al. (1985) reported cloning of the ALDH1 and ALDH2 genes. The 2
proteins showed 69% homology at the protein level. The ALDH1 gene
encodes a 501-residue protein (Hsu et al., 1989).
MAPPING
With cDNA probes for Southern blot analysis of somatic cell hybrids, Hsu
et al. (1985, 1986) assigned the ALDH1 locus to chromosome 9q and the
ALDH2 locus to chromosome 12.
GENE STRUCTURE
Hsu et al. (1989) found that the ALDH1 gene is about 53 kb long and is
divided into 13 exons. A similar intron-exon organization was found in
ALDH2, which also has 13 exons with 9 of the 12 introns interrupting the
coding sequence at positions homologous to those in ALDH1. Thus, the 2
isozymes appear to have evolved after duplication of a common ancestral
gene.
MOLECULAR GENETICS
Thomas et al. (1982) found low cytosolic ALDH in the liver of alcoholic
patients with fatty liver; mitochondrial ALDH was normal. Abstaining
alcoholics showed persistently low cytosolic ALDH.
Eckey et al. (1986) reported a variant of cytosolic ALDH in a Chinese
autopsy liver specimen. While the major isozyme band was nearly absent,
several additional minor bands were observed on isoelectric focusing
gel. Rabbit antibodies showed immunological cross-reactivity for the
variant enzyme bands. The existence of additional minor bands indicated
the presence of tetramer hybrid forms made up of normal and variant
monomers. The observed abnormality may represent a heterozygous form of
cytosolic ALDH variation. A similar variant was also detected in
erythrocytes of a male Thai student.
Yoshida et al. (1989) demonstrated that among Caucasians alcohol
flushing can be related to abnormalities of ALDH1. In 9 unrelated
Caucasian alcohol flushers, they found 1 who exhibited low activity
(10-20% of normal) and another who exhibited moderately low activity
(60%) and altered kinetic properties. The electrophoretic mobilities of
these 2 samples were not altered. Immunologic quantitation indicated
that the amount of protein in the 2 samples was not reduced in parallel
with the enzyme deficiency. In the first case, the daughter of the
proposita also had very low enzyme activity and alcohol flushing.
ANIMAL MODEL
Retinaldehyde is generated by ADH1 (103700) from retinol, and its
concentration is determined in large part by its subsequent catabolism
by RALDH1 to retinoic acid. Ziouzenkova et al. (2007) demonstrated that
retinaldehyde is present in rodent fat, binds retinol-binding proteins
(CRBP1, 180260; RBP4, 180250), and suppresses PPARG (601487) and
retinoid X receptor (see 180245) responses. Raldh1 -/- mice resisted
diet-induced obesity and insulin resistance and showed increased energy
dissipation. In ob/ob (see 164160) mice, administering retinaldehyde or
a Raldh inhibitor reduced fat and increased insulin sensitivity.
Ziouzenkova et al. (2007) concluded that retinaldehyde is a distinct
transcriptional regulator of the metabolic responses to a high-fat diet.
*FIELD* RF
1. Eckey, R.; Agarwal, D. P.; Saha, N.; Goedde, H. W.: Detection
and partial characterization of a variant form of cytosolic aldehyde
dehydrogenase isozyme. Hum. Genet. 72: 95-97, 1986.
2. Hempel, J.; von Bahr-Lindstrom, H.; Jornvall, H.: Aldehyde dehydrogenase
from human liver: primary structure of the cytoplasmic isoenzyme. Europ.
J. Biochem. 141: 21-35, 1984.
3. Hsu, L. C.; Chang, W.-C.; Yoshida, A.: Genomic structure of the
human cytosolic aldehyde dehydrogenase gene. Genomics 5: 857-865,
1989.
4. Hsu, L. C.; Tani, K.; Fujiyoshi, T.; Kurachi, K.; Yoshida, A.:
Cloning of cDNAs for human aldehyde dehydrogenases 1 and 2. Proc.
Nat. Acad. Sci. 82: 3771-3775, 1985.
5. Hsu, L. C.; Yoshida, A.; Mohandas, T.: Chromosomal assignment
of the genes for human aldehyde dehydrogenase-1 and aldehyde dehydrogenase-2. Am.
J. Hum. Genet. 38: 641-648, 1986.
6. Inoue, K.; Nishimukai, H.; Yamasawa, K.: Purification and partial
characterization of aldehyde dehydrogenase from human erythrocytes. Biochim.
Biophys. Acta 569: 117-123, 1979.
7. Thomas, M.; Halsall, S.; Peters, T. J.: Role of hepatic acetaldehyde
dehydrogenase in alcoholism: demonstration of persistent reduction
of cytosolic activity in abstaining patients. Lancet II: 1057-1059,
1982.
8. Yoshida, A.; Dave, V.; Ward, R. J.; Peters, T. J.: Cytosolic aldehyde
dehydrogenase (ALDH1) variants found in alcohol flushers. Ann. Hum.
Genet. 53: 1-7, 1989.
9. Ziouzenkova, O.; Orasanu, G.; Sharlach, M.; Akiyama, T. E.; Berger,
J. P.; Viereck, J.; Hamilton, J. A.; Tang, G.; Dolnikowski, G. G.;
Vogel, S.; Duester, G.; Plutzky, J.: Retinaldehyde represses adipogenesis
and diet-induced obesity. Nature Med. 13: 695-702, 2007.
*FIELD* CN
Marla J. F. O'Neill - updated: 7/2/2007
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
ckniffin: 10/21/2009
terry: 1/7/2009
wwang: 7/5/2007
terry: 7/2/2007
alopez: 2/3/2006
mgross: 11/19/2001
carol: 4/3/2001
dkim: 7/17/1998
dkim: 6/26/1998
jenny: 7/2/1997
jenny: 7/1/1997
mimadm: 3/11/1994
supermim: 3/16/1992
carol: 2/29/1992
supermim: 3/20/1990
carol: 12/14/1989
carol: 11/2/1989